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Transcriptome sequencing identifies prognostic genes involved in gastric adenocarcinoma

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Abstract

Gastric adenocarcinoma (GAC) is one of the world's most lethal malignant tumors. It has been established that the occurrence and progression of GAC are linked to molecular changes. However, the pathogenesis mechanism of GAC remains unclear. In this study, we sequenced 6 pairs of GAC tumor tissues and adjacent normal tissues and collected GAC gene expression profile data from the TCGA database. Analysis of this data revealed 465 differentially expressed genes (DEGs), of which 246 were upregulated and 219 were downregulated. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis demonstrated that DEGs were observably enriched in ECM-receptor interaction, protein digestion and absorption, and gastric acid secretion pathways. Six key genes (MATN3, COL1A1, COL5A2, P4HA3, SERPINE1 and VCAN) associated with poor GAC prognosis were screened from the protein‒protein interaction (PPI) network by survival analysis, and P4HA3 and MATN3 have rarely been reported to be associated with GAC. We further analyzed the function of P4HA3 in the GAC cell line SGC-7901 by RT‒qPCR, MTT, flow cytometry, colony formation, wound healing, Transwell and western blot assays. We found that P4HA3 was upregulated in the SGC-7901 cell line versus normal control cells. The outcomes of the loss-of-function assay illustrated that P4HA3 significantly enhanced the ability of GAC cells to proliferate and migrate. This study provides a new basis for the selection of prognostic markers and therapeutic targets for GAC.

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Funding

This work was supported by the Natural Nature Science Foundation of China (81700709), Research Foundation of Jilin Provincial Science & Technology Development (20180520105JH), Systems Biology Research on Genome and Transcriptome of Stem Cells (2017030) of Jilin Province Sunbird Regenerative Medical Engineering Co., Ltd.

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  1. Mingyue Li and Miao Bai contributed equally to this work.

Authors and Affiliations

  1. National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun, 130024, China

    Mingyue Li, Yulun Wu, Shuo Yang, Lihua Zheng, Luguo Sun, Chunlei Yu & Yanxin Huang

  2. National and Local Joint Engineering Research Center of Storage, Processing and Safety Control Technology for Fresh Agricultural and Aquatic Products, Bohai University, Jinzhou, 121013, China

    Miao Bai

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  1. Mingyue Li
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Contributions

Concept and design: ML, LS, CY, YH. Bioinformatics analysis: ML, MB. Biological assays: ML, MB, YW, SY, LZ. Drafting, revision and final approval of the manuscript: ML, MB, YW, SY, LZ, LS, CY, YH.

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Correspondence to Yanxin Huang.

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Li, M., Bai, M., Wu, Y. et al. Transcriptome sequencing identifies prognostic genes involved in gastric adenocarcinoma. Mol Cell Biochem 478, 2891–2906 (2023). https://doi.org/10.1007/s11010-023-04705-3

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